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Mice with Circadian Defect Show Mania-Like Symptoms

Study suggests changes in daily rhythm may affect bipolar disorder in humans

FRIDAY, March 23 (HealthDay News) -- Mice carrying a mutation in the circadian rhythm-regulating Clock gene show signs of mania, supporting the role of this gene, and daily rhythms in general, in regulating mood and behavior in humans, according to a report published online March 22 in the Proceedings of the National Academy of Sciences Early Edition.

Since abnormalities in circadian rhythm may contribute to the manic component of bipolar disorder, Colleen McClung, Ph.D., of the University of Texas Southwestern Medical Center in Dallas, and colleagues examined the behavior of mice with a mutation in the central transcriptional activator of molecular rhythms, Clock.

The investigators found that Clock-mutant mice exhibited behavior strikingly similar to mania in humans, including hyperactivity, decreased sleep, and an increase in the reward value for cocaine and sucrose. Chronic treatment with lithium, which helps stabilize mood in humans with bipolar disorder, returned the behavioral responses in the mutant mice to more normal-type activity.

"These findings establish the Clock-mutant mice as a previously unrecognized model of human mania and reveal an important role for CLOCK in the dopaminergic system in regulating behavior and mood," the authors write.

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